DISCLAIMER: The cases / examples on this blog have been anonymised to maintain confidentiality of patients. Cases have been acquired from various international hospitals and through other medical colleagues with the intention to teach through case examples.

Wednesday, 28 November 2007

Yesterday was the 3rd combined US Navy medical meeting with our institution.

The session started off with one of our excellent English speaking first year resident's, Dr Tsunoda., who presented a case of a young patient with a history of what appeared to be consistent with meningitis. The case took a twist as the patient had an additional problem of an abnormality in the left frontal lobe on CT scanning which was considered by some to be a contusion and by other to be an abscess or even a lymphoma.This was a so-called 'Grey Case' as there was no definite answer, but it provided an excellent opportunity to raise discussion on the possibilities that existed for generation of a differential diagnosis and work-up of the patient.

Following on in the second half, a US Navy resident, Dr Suzuki, presented a case of a patient with diffuse arthralgia & tenosynovitis and skin lesions on the hands and feet. The case took on a whole new slant when a sexual history was enquired about and the diagnosis unravelled nicely just based on this set of questions. The patient had had risky sexual encounters. The senior members of our institution got the diagnosis just based on the history, but particularly the new element of a strong sexual history, and a few photos of the skin lesions. I was very proud to hear them say-- disseminated neisseria gonorrhoea and the diagnosis was later confirmed as this.

By grouping together the significant parts of the history such as sexual exposure, arthralgia & tenosynovitis and skin lesions made the diagnosis relatively straight forwards.

It was interesting to hear that the rate of gonorrhoea infection in Japan may in fact be higher in prevalence than in the USA ! Moreover, cultures to try and identify the organism are usually negative! Hence, a high suspicion of this infection needs to be borne in mind.

The evening went very well and the cases presented made us all think and they provided a great forum for discussion.

As I emphasize on many occasions, take a sexual history. Being married is not the beginning and the end of a sexual history. Probing deeper about sexual partners, foreign travel for sex, types of sexual encounter e.g. bisexual, types of sex e.g. oral, anal, are very important and should be pursued in your questioning especially if you think that the problem is a sexually transmitted infection. In knowing the answers to the above allows one to consider which places to examine and where to obtain cultures.

Moreover, contact tracing for partners is essential as part of a well organised public health programme because stopping the spread of sexual infections such as HIV, gonorrhoea, syphilis and chlamydia and education on safer sexual practices will hopefully reduce some of these most devastating infections known to mankind.

Tuesday, 27 November 2007

This case is a great example of how to work up a Medical Patient and it shows how being too specialised in ones approach can cause the physician to lose sight of the bigger picture. This case wins by the fact that a senior doctor did not lose focus of all the medical problems and considered a unifying diagnosis under the principles of William of Okham, so-called Okham's Razor.

Case

An elderly gentleman was admitted into a hospital with a 6 month history of Gynaecomastia.

He had noticed breast enlargement and tenderness six months previously at which time it was noted that it was probably due to the spironolactone used for his heart failure and the drug was subsequently stopped. He had no galactorrhoea.

However, the gynaecomastia did not improve, so his local hospital measured the serum prolactin level which was found to be mildly raised (approximately 1.5 x normal) and he was sent to another hospital for more intensive investigation.

However, one week before admission to the next hospital, whilst walking, he developed sudden onset of lower back pain. The pain remained even at night and stopped him from sleeping. He was then having difficulty walking because of it.

On further questioning, Body Systems Review revealed a problem with urination as it took him some 5 minutes to void his urine. Moreover, he had no had an penile erection in 10 years. He had not lost any body hair although he had never had a lot in the past.

Body Systems Review also revealed no loss or change in vision and no headaches, nausea or vomiting.

Cardiovascular examination revealed a pulse of 80 per minute and regular. JVP was raised to the angle of the jaw and showed a systolic 'v' wave consistent with Tricuspid Regurgitation. No murmur could be identified. No leg oedema was seen.

Abdominal examination revealed a slightly distended abdomen that was soft and non-tender with no abdominal masses. Bowel sounds were present. There were no hernial orifices and no AAA. Rectal examination had not been done !!! :-(

Neurological examination of the Lower Limbs was abnormal. Straight leg raising caused pain on the right leg at 70 degrees but immense pain of the left side at only 30 degrees-- a positive test.

The patient was unable to raise legs spontaneously due to pain. Reflexes showed hyper-reflexia throughout in upper and lower limbs but were absent at the ankles. Babinski sign was normal bilaterally. L5 dermatome on the left lower limb revealed loss of sensation (skin sensation below the knee).

CNS examination revealed normal cranial nerves throughout and there was no evidence of bitemporal hemianopia.

Examination of the lower spine was not painful to touch.

Lab data revealed a normal CBC, Normal Na & K but BUN was 50 and Creat 1.6.Liver function was normal.Calcium was 10.6 (mildly elevated)Prolactin level was 1.5 times normal.Thyroid function was normalFSH/LH were 20-30 times normal and testosterone was low normalCortisol, GH and ACTH were normal.

CXR revealed a small area of scarring at the lateral right upper zone consistent with old TB but no evidence of malignancy.

Clinical Impression From History & Examination and Lab Data

Okay, this patient had in fact been admitted into hospital for a TRH stimulation test because of the raised prolactin. The back problem had not been known about until the patient had been admitted and had complained of the problem.

This patient therefore had several problems

Gynaecomastia and Hyperprolactinaemia

Renal Failure

Hypercalcaemia (mild)

Back pain of sudden onset with Lower Motor Neurone Signs.

Probable Tricuspid Regurgitation

High LH/FSH and low-normal testosterone (testicular failure)

In this case, I think the patient has developed gynaecomastia from hyperprolactinaemia and spironolactone. But, the drug was stopped. Prolactin can be raised for several reasons but most people immediately think Pituitary Tumour and do a reflex MRI head scan. Well, in view that the LH / FSH levels are high as well, one might naturally think it to be a pituitary source. However, pituitary adenomas in males present LATE and are usually macroadenomas (>10mm in size) and tend to cause Visual Disturbance. This patient had no obvious visual impairment.The Raised LH and FSH should have caused a raised testosterone level, but they did not in this case because of the low-normal level (which is inappropriately low) thereby suggesting Testicular Failure.

In Testicular Failure, in response to low testosterone levels, the feedback loop of the pituitary axis is for LH and FSH to rise. Hence, the rise in these levels is unlikely to be due to a tumour. Moreover, LH-FSH secreting pituitary adenomas are rare. Also, prolactin when raised to very high levels e.g. 20x normal with prolactin secreting adenomas, there is inhibition of LHRH and reduction in LH & FSH; hence, in this case, with LH and FSH being high, it was unlikely to be caused by an adenoma. The fact that the other anterior pituitary hormones were left intact goes against panhypopituitarism.

History was important here because on Body System Review, it was elucidated that the patient had had no sexual activity in 10 years due to erectile failure, which again would fit with Testicular Failure. This patient did not offer the information of erectile failure spontaneously, but it was the clever junior doctor that asked the question and the patient then was able to answer to the affirmative.

The raised prolactin from a Prolactinoma, I would expect to be higher and as I say, I would expect some visual disturbance because of the nature of the presentation of pituitary adenomas in men.

However, one obvious cause of hyper-prolactinaemia is Hypothyroidism because of raised TRH in response to low T3/T4 also drives Prolactin release. In this case, all thyroid function was normal. Hence, it was not entirely clear why a TRH stimulation test was being performed at all. Some authorities advocate a TRH stimulation test, but it does not really tell you what or where the problem is. A TRH stimulation test is perhaps more useful when combined with a LHRH and insulin stress test for patients with suspected hypopituitarism, usually performed post-operatively for pituitary adenomas.

Perhaps, the most obvious cause of the Prolactin being elevated was renal failure induced by the Candesartan (ARB) plus furosemide [dry skin, reduced skin turgor].

There are numerous causes of hyperprolactinaemia which are detailed in any good textbook and are beyond the scope of today's talk.

Now, why did this patient get back pain?? Well, hypotestosteronaemia in men can result in osteoporosis. Referring back to the history, this patient was walking when he suddenly developed severe back pain. This suggests either a vertebral fracture or intervertebral disc herniation. One always has to considered serious causes of neurology such as cauda equina syndrome whereby the lower spinal nerves roots become compressed in a lower motor neurone distribution. Even worse is the conus medullaris syndrome with compression of the spinal cord that can lead to permanent paralysis of one or both lower limbs. In such conditions, patients can develop urinary problems such as retention and then overflow and hence, incontinence and the same can occur with the bowel giving constipation and then overflow diarrhoea.

That is why a rectal examination is so important !!! Rectal examination should always be done in patients with back pain and abnormal neurology affecting the lower limbs.

In this situation, it is useful to check TONE by asking the patient to squeeze with their anus on the examiners finger. Loss of tone is an ominous clinical sign. Moreover, checking sensation around the anus for numbness is also suggestive of a compression problem.

Rectal examination is also important in this case to identify possible prostate cancer as it might also account for the prolonged micturition symptoms and if metastatic, could result in a vertebral fracture.

Hence, a senior doctor who saw this patient suggested the possible diagnoses

Iatrogenic Renal failure with secondary Hyper-Prolactinaemia

Testicular Failure with Hypotestosteronaemia, raised LH and FSH

Osteoporotic fracture due to hypotestosteronaemia

Lower motor neurone signs of the left lower limb due to nerve impingement syndrome from likely intervertebral disc herniation

However, a pituitary adenoma would have needed to be ruled out by MRI head scan but in view of the previous insertion of coronary artery stents, the patient could not have such imaging. A CT head scan was not performed.

Results

Lumbar Xray did confirm a new vertebral disc fracture at the T12 position when compared to Xrays taken several months before and this 'biopsy' of the radiological archives indicated that he had been experiencing back pain for some time, although it had worsened on this admission due to the new fracture.The ARB and furosemide were stopped with some improvement of the renal failure.Moreover, PSA and a Myeloma Screen [renal failure, raised calcium and back pain] should also have been checked in view of being elderly and male.The patient's back pain improved during the admission and there was no weakness of the lower limbs and he was subsequently discharged home for follow-up as an outpatient.

In summary,

Not all hyperprolactinaemia is due to an adenoma. Think of more common things e.g. drug induced renal failure, anti-dopaminergic drugs, lung cancer

If you find back pain you must examine the neurology of the lower limbs, check sensation and do a rectal examination. Such patients require urgent imaging by Xray and MRI and may require urgent neurosurgery.

Remember, drugs can cause renal failure and the drugs should always be examined in detail and if there is a concern that they are the cause, they should be STOPPED. As in this case, the patient also had COPD and was also taking two bronchospasm-promoting drugs !!! e.g. aspirin and a beta-blocker. Other drugs such as ticlopidine / clopidogrel can be used in place of aspirin and beta-blockers used for hypertension can be switched to other classes such as a calcium channel blocker. If used for anti-arrhythmic purposes there are many agents out there that can be used in place of a beta-blocker.

Remember to Ask Questions from Body Systems Review- you will find symptoms that the patient never thought were a problem and that they never thought you would ask and it will save your patient and you too.

Men with osteoporosis due to hypotestosteronaemia may benefit from testosterone replacement and reduction of fractures with the use of bisphosphonate drugs or the newer recombinant human parathyroid hormone ( teraparatide ), which should be strongly considered in this case. Note: when starting testosterone therapy, prostate cancer should be initially ruled out because hormone therapy can accelerate this type of cancer.

Most compression neuropathies from intervertebral disc herniation improve with time, but if severe e.g. severe pain, loss of function, then disc surgery should be considered.

Remember,Rectal Examination, Rectal Examination and finally, Rectal Examination. Never Forget to Do It !!!!!!!!

In view that this patient had biochemical evidence of testicular failure, the genitalia should have also been examined. Never forget to examine this area.

Monday, 26 November 2007

A 70 year old female was admitted into another hospital in Japan, following 3 episodes of gastrointestinal haemorrhage.

She had first noticed dark, black stool the day before admission and she had slight lower abdominal discomfort.However, by the next day, this was followed by fresh red blood on defecation. There was no information about how much bloody stool was produced.

The patient had no other symptoms including no nausea, haematemesis, vomiting, epigastric pain, dizziness, dyspnoea, palpitations etc...

The patient had known severe coronary artery disease and had had a previous myocardial infarction resulting in 100% stenosis of the RCA, LCX arteries and a patent LAD which housed a stent to maintain its patency. Not only that, an apical thrombus had been diagnosed due to dyskinesis of the left ventricle, several months before for which anticoagulation was used.

The patient was also receiving aspirin and ticlopidine but no proton pump inhibitor (PPI).

The patient was not using alcohol. There was no history of any previous GI complaint.

Previous medical history apart from the above also included Diabetes Mellitus (Type 2) for which a sulphonylurea was used for control.

She was a non-smoker.

On examination the patient looked unwell and pale. The blood pressure was 80/40 despite having received 3 litres of crystalloid fluid. Pulse was 120/min and regular. Temp 37.0Resp Rate 14/min and O2 sats 97% on room air.

CVS: Pulse quality was reduced at the radial artery; it was difficult to find. Left hand middle and ring fingers were cold to touch. JVP was not elevated. No heaves or thrills. Heart sounds were normal. No peripheral oedema was found.

One area with highest risk from bleeding was the Upper GI tract such as the stomach or duodenum in view of the history of anti-platelet agents and malaena, although lower GI haemorrhage could not be totally excluded because of the lower abdominal discomfort that was non-specific. Sometimes, a caecal focus of bleeding can produce stool that looks similar to malena. A raised BUN to Creatinine ratio can signify upper GI haemorrhage but in this case it might also be as a result of renal hypoperfusion from shock-- there is simply no way to accurately tell unless a gastroscopy is performed !

However, this patient was not straight forwards because despite the bleeding, by reversing the coagulation might result in either stent thrombus or embolisation of the apical thrombus. This is a so-called Catch 22 situation i.e. you cannot win either way. You are damned if you do and damned if you don't..... :-(

It was clear that by not reversing the coagulation disturbance the patient would exsanguinate.

A senior doctor who reviewed the patient was suspicious that the combination of warfarin plus two anti-platelet agents was the cause for the bleeding. It was suggested that the following things should be instituted:

Blood replacement to aim for an Hb>10g/dl especially as coronary heart disease

Urgent gastroscopy and colonoscopy. The former was suggested because of the raised BUN to Creatinine ratio.

Insert a Foley catheter to measure hourly urine output

Aim for systolic BP >100mmHg

Repeat echocardiogram

However, in the end, only Vitamin K was used and only a colonoscopy was performed which is shown below:

The colonoscopy showed generalised mucosal bleeding suggesting platelet dysfunction and coagulation disturbance. There was also evidence of Diverticular disease with bleeding, and although it is common for these to bleed, it by itself does not account for the generalised bleeding. Thus, the bleeding had resulted from an iatrogenic source-- DRUGS!

A gastroscopy was not performed and hence, an upper GI bleed was never excluded here.

Repeat transthoracic echocardiogram revealed that the thrombus located at the apex had become smaller in size as one would expect on treatment.

In this case, what one has to decide is which problem is going to be immediately life threatening, in this case, GI haemorrhage. Hence, once the bleeding had been stopped e.g. by clipping bleeding vessels and stopping harmful drugs temporarily e.g. aspirin, ticlopidine and warfarin andreversing coagulation disturbance, then treatment to prevent stent thrombosis / thromboembolisation would be the next step.

In view that the thrombus had reduced in size (and was more likely to be organising) and that with time, stent thrombosis is relatively less compared to the time when they are initially inserted, the relative risk of thrombosis/embolisation versus uncontrolled haemorrhage tipped the scales in favour of concentrating on stopping bleeding first. Remember the emergency ABC- without a Circulation the heart will have no blood supply for itself or for the rest of the body! Hence, stopping bleeding and maintaining the circulation is essential.

There were certain areas with this cases where management could have been optimised, for example:

Performing Gastroscopy to exclude an upper GI source of haemorrhage (remember, there was malaena too and raised BUN/creatinine ratio!)

Use of FFP-- essential. Reversing the INR (in this case, probably an incomplete reversal of INR would suffice) until all bleeding had ceased then followed by intravenous heparin for cardiac protection. Use of heparin is preferred in such circumstances because if bleeding recurs, the heparin can be immediately stopped and if need be, protamine sulphate can be used to reverse it. The only concerns here would be recurrent bleeding and the potential Heparin-Induced Thrombocytopaenia. HIT does not happen immediately and the risk increases the longer the heparin is used, usually over several days to weeks.

Vitamin K was used which would have returned the INR to near normal although it takes several hours for new clotting factors to come into play and this might be too late for someone bleeding rapidly. Always consider using FFP. FFP contains pre-formed clotting factors and hence, it will temporarily normalise the INR whilst Vitamin K allows new intrinsic clotting factors to be produced.

Hence, the idea that hoping to maintain a high INR for coronary protection and at the same time clipping bleeding areas in the face of generalised mucosal bleeding that could result in multiple torrential sites of bleeding at any time and anywhere needs a re-evaluation. It is like trying to plug holes in a kitchen sieve- a self-defeating objective.Not performing a gastroscopy again needs reconsidering because this patient had generalised mucosal bleeding and was probably bleeding from every part of the GI tract.

Remember, it is not just GI tracts that bleed on warfarin with dysfunctional platelets, anywhere can bleed, but especially the brain. The GI tract is a good guide (and the skin too) to know what is going on with coagulation in the rest of the body and with mucosal bleeding then be warned because your patient could have a intracerebral bleed.The important thing here was to control the clotting first and thereby control the bleeding to make the patient haemodynamically stable and then image the GI tract and then consider starting the heparin to protect the heart.

In this case, the patient's INR was reduced to 1.4 on Vitamin K alone and the repeat colonoscopy reconfirmed multiple areas of previous haemorrhage.

These kinds of case are not described in your average medical text book as no case is the same as the next.Doctors should always expect the unexpected and hope for the best, but plan for the worse. An element of uncertainty is always going to occur in a case such as this, and sometimes, keeping your nerve and following long-upheld evidence based rules but at the same time taking a leap of faith into the unknown is required in order to help your patient.